Rotatable fluid sample collection device

ABSTRACT

A sample collection device for a fluid sample includes: a body including a capillary channel having a first end and a second end, wherein the first end is adapted to draw the fluid into the channel by capillary action; an air vent located in the vicinity of the second end and in fluid communication with the capillary channel; a barrier positioned within the capillary channel to prevent flow of the fluid by capillary action thereacross; and features on opposing sides of the body to form an axis of rotation, which is substantially perpendicular to the overall direction of the capillary channel from the first end to the second end. In a preferred embodiment, the sample collection device is adapted to rotate about the axis of rotation within a cartridge having a sample manipulation device to bring the first end into position with the sample manipulation device.

CROSS REFERENCE TO RELATED APPLICATIONS

This patent application claims priority to U.S. Provisional ApplicationNo. 61/791,334, filed Mar. 15, 2013, the disclosure of which isincorporated by reference in its entirety.

FIELD OF THE INVENTION

This present invention relates to a device for use in collecting andstoring fluid samples, particularly biological samples, such as whole(unseparated) blood, serum, plasma and urine taken from the human oranimal body. Such biological samples may be used in diagnostic and otherbiochemical tests. More particularly, the present invention relates tosuch a device which relies on capillary action for the collection of thefluid sample. The invention also relates to a working element comprisingthe fluid sample collection device. The present invention also relatesto the field of diagnostic assays, and in particular to lateral flowassays where an analyte to be detected is present in a biologicalsample.

BACKGROUND

Fluid samples taken from the human or animal body are required for awide variety of diagnostic and other biochemical tests, including themeasurement of immunological reactions (immunoassays). There isaccordingly a need for a device which can be conveniently used forcollecting and storing such samples. Since the samples may pose amicrobiological contamination or heath risk, the device used for theircollection should not allow unintended release of the samples duringstorage, transportation or manipulation. The sample collection device ispreferably disposable.

A known sample collection device for whole blood comprises an open-endedlinear capillary tube formed of glass. The tube typically has aninternal diameter of between one and two millimeters. To preventclotting of the collected blood, the internal surface of the tube may becoated with a suitable anticoagulant such as heparin, which may alsoserve to reduce the contact angle between the sample and the side of thetube.

In use of the known device, the skin on the tip of a patient's finger ispierced by a lancet or other sharp piercing member. The blood soelicited is drawn into the linear tube by capillary action. The volumeof the blood sample and the rate at which it is collected may bemaximized by holding the tube with a generally horizontal orientation.The volume of the sample collected in this way is usually of the orderof 25-100 μL.

A problem associated with the blood sample collection device describedabove relates to the transportation and handling of the samplesubsequent to its collection. In particular, when the orientation of thelinear tube is changed, there is a risk that gravitational forces actingon the sample may exceed the intermolecular forces which maintain thesample in the tube, leading to the unintended release of a portion ofthe sample and the associated microbiological contamination or heathrisk. This problem may be exacerbated when the linear tube is alsosubjected to accelerations caused by sudden movements or decelerationscaused by small knocks, etc.

To prevent the unintended release of the sample, it is known to stopperone or both ends of the linear capillary tube, for example usingsilicone bungs or sealant. However, there remains a risk that a portionof the sample may be accidentally released before the ends of the tubehave been sealed or after the seal has been removed for subsequentprocessing.

There are many challenges in designing a sample collection device to beuse in conjunction with further sample manipulation such as diagnostictesting. These include: minimizing contamination due to prematuredispense or leakage from the sample collection device; enablingcollection directly from a patient (i.e., finger stick) as well as fromperipheral sample collection devices such as collection tubes orsyringes; insufficient transfer of the sample to the manipulationdevice; ensuring collection volume is sufficient for the samplemanipulation process; sample evaporation; minimizing the ability tore-open the sample collection device to avoid contamination; or othersources of inaccuracies in the sample manipulation process. Thus, thereis a need in the art for an improved sample collection device for thatovercomes the problems of the known art described above. In particularthere is a need in the art for an improved sample collection device,which fluids are generally aqueous, and particularly such a device forwhich the risk of accidentally release of a portion of the samplesubsequent to its collection may be reduced.

SUMMARY OF THE INVENTION

The present invention is directed to an assay device that alleviates oneor more the foregoing problems described above.

One aspect of the invention is directed to a sample collection devicefor a fluid sample, the device comprising: a body including a capillarychannel having a first end and a second end, wherein the first end isadapted to draw the fluid into the channel by capillary action; an airvent located in the vicinity of the second end and in fluidcommunication with the capillary channel; a barrier positioned withinthe capillary channel to prevent flow of the fluid by capillary actionthereacross; and features on opposing sides of the body to form an axisof rotation, which is substantially perpendicular to the overalldirection of the capillary channel from the first end to the second end.In a preferred embodiment, the sample collection device is adapted torotate about the axis of rotation within a cartridge having a samplemanipulation device to bring the first end into position with the samplemanipulation device.

Another aspect of the invention is directed to a working elementcomprising: a sample collection device for a fluid sample, the devicecomprising: a body including a capillary channel having a first end anda second end, wherein the first end is adapted to draw the fluid intothe channel by capillary action; an air vent located in the vicinity ofthe second end and in fluid communication with the capillary channel; abarrier positioned within the capillary channel to prevent flow of thefluid by capillary action thereacross; and features on opposing sides ofthe body; and a cartridge having a sample manipulation device, whereinthe cartridge has features that correspond to features on the samplecollection device to form an axis of rotation, which is substantiallyperpendicular to the overall direction of the capillary channel from thefirst end to the second end about which the sample collection devicerotates, and wherein the sample collection device is adapted to rotateabout the axis of rotation to bring the first end into position with thesample manipulation device. In a preferred embodiment, the samplemanipulation portion is an analytical chamber having an analyticalreagent thereon, such as a lateral flow assay device.

Still another aspect of the invention is directed to a method forcollecting a fluid sample comprising: providing a working elementdescribed above; rotating the sample collection device to position thefirst end in a direction extending away from the cartridge; bringing thefirst end into contact with the sample, whereby capillary action drawsthe sample into the channel and to the barrier; rotating the samplecollection device to position the first end into position with thesample manipulation device; and applying air pressure to the air vent toforce the sample across the barrier and into contact with the samplemanipulation device.

Yet another aspect of the invention is directed to a method ofperforming an assay on a liquid sample for the presence or concentrationof one or more analyte(s) or control(s), on the assay device describedabove, comprising: rotating the sample collection device to position thefirst end in a direction extending away from the cartridge; bringing thefirst end into contact with the sample, whereby capillary action drawsthe sample into the channel and to the barrier; rotating the samplecollection device to position the first end into position with assaydevice; applying air pressure to the air vent to force the sample acrossthe barrier and into contact with a sample addition zone of the assaydevice; moving the sample by capillary action through a fluid flow pathinto a reagent zone where it dissolves one or more reagents; flowing thesample away from the reagent zone having a dissolved reagent plumecontaining one or more reagents and into detection zone(s) by capillaryaction through the fluid flow path, wherein signal(s) representative ofthe presence or concentration of analyte(s) or control(s) is produced;and reading the signal(s) that are produced in the detection zones todetermine the presence or concentration of the analytes or controls.

Further objects, features and advantages of the present invention willbe apparent to those skilled in the art from detailed consideration ofthe preferred embodiments that follow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a perspective view of a sample collection device accordingto one embodiment of the invention.

FIG. 2A shows a perspective view of the working element including thesample collection device in sample collection position according to oneembodiment of the invention.

FIG. 2B shows a perspective view of the working element including thesample collection device in sample dispense position according to oneembodiment of the invention.

FIG. 3A shows a top planar view of the working element including thesample collection device in sample dispense position according to oneembodiment of the invention.

FIG. 3B shows a top planar view of the working element including thesample collection device in sample collection position according to oneembodiment of the invention.

FIG. 4 shows a perspective view of the working element including thesample collection device positioned between a sample collection positionand sample dispense position according to one embodiment of theinvention.

FIG. 5 shows a perspective view of the working element not including thesample collection device according to one embodiment of the invention.

FIG. 6 shows an embodiment of an assay device usable in the presentinvention.

FIG. 7 shows another embodiment of an assay device usable in the presentinvention.

FIG. 8 shows another embodiment of an assay device usable in the presentinvention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

As used in this specification and the appended claims, the singularforms “a”, “an” and “the” include plural referents unless the contextclearly dictates otherwise.

The term “about” as used in connection with a numerical value throughoutthe description and the claims denotes an interval of accuracy, familiarand acceptable to a person skilled in the art. The interval ispreferably ±10%.

The term “sample” herein means a volume of a liquid, solution orsuspension, intended to be acted upon by a sample manipulation device.In a preferred embodiment, the sample is subjected to qualitative orquantitative determination of any of its properties, such as thepresence or absence of a component, the concentration of a component,etc. Typical samples in the context of the present invention are humanor animal bodily fluids such as blood, plasma, serum, lymph, urine,saliva, semen, amniotic fluid, gastric fluid, phlegm, sputum, mucus,tears, stool, etc. Other types of samples are derived from human oranimal tissue samples where the tissue sample has been processed into aliquid, solution, or suspension to reveal particular tissue componentsfor examination. The embodiments of the present invention are applicableto all bodily samples, but preferably to samples of whole blood, urineor sputum.

In other instances, the sample can be related to food testing,environmental testing, bio-threat or bio-hazard testing, etc. This isonly a small example of samples that can be used in the presentinvention.

Non-biological samples can be aqueous or non-aqueous, for example wastewater samples for environmental testing and solutions having organicsolvents, such as alcohols for chemical processing. One aspect of theinvention is directed to a sample collection device for collecting asample, such as a blood or blood-based sample, and delivering it to asample manipulation device that overcomes at least some of thedisadvantages of known sample collection devices.

FIG. 1 shows a preferred embodiment of the sample collection device 10.The device includes a body 10A having a preferably substantiallyrectangular shaped as shown in FIG. 2A having a thickness “x”. The bodymay be rounded or beveled at its edges as shown by reference number 16.In a particularly preferred embodiment the device may have wings or tabs17A and 17B (see FIG. 1) extending from the sides of the device to aidin rotating or flipping the device as described below. While the body ofthe device is preferably rectangular shaped, any shape can be used aslong as it has dimensions capable of holding a sufficient amount ofsample and can be rotated or flipped. The sample collection device canbe made from any suitable material, such as a plastics material, such aspolymethyl methacrylate (other plastic materials can includepolystyrene, polyethylene, cyclic olefins, acrylics, or moldablepolyesters), and is preferably formed by molding such as injectionmolding. Other possible materials include glass, metal ceramic, etc. Thetabs 17A and 17B can be molded or formed together with the body 10A toform one unitary piece. Alternatively, the tabs can be separatelyapplied, such as by adhesive. In a preferred embodiment, the device isat least partially transparent such that the flow of the fluid in thecapillary channel can be observed.

Positioned within the body is a capillary channel 11 having dimensionssufficient to hold a desired amount of sample. The capillary channel mayhave any cross-sectional shape, for example circular or substantiallysemi-circular (“U” shaped) cross-sections. A substantially semi-circularcross-sectional shape is particularly convenient if the channel is to bedefined between two flat components in contact with each other, sinceonly one of the components then needs to be grooved. FIG. 1 shows aparticularly preferred embodiment, where the body is made of two flatpieces that are joined together to form the capillary channel. FIG. 1shows the device with both of the pieces joined. In this embodiment, thetop piece 15A is joined to the bottom piece 15B, such as by an adhesive.The top piece is preferably a hydrophilic tape. The dimensions of thechannel are selected such that capillary flow of the fluid being sampledwill be achieved. For a biological sample, such as blood or plasma, thechannel will preferably have a cross-section that is in the range of0.25-3.0 mm², preferably 0.5-3.0 mm². The volume of the capillarychannel may be in the range 10 μL to 100 μL, preferably in the range 10μL to 70 μL, and more preferably 20 μL to 50 μL. The length of thecapillary channel is preferably 20 mm-100 mm. For aqueous samples, thecapillary channel is preferably treated to render the surfacehydrophilic, if it is not already. In addition, for biological samples,such as whole blood, other additives can be included to preserve thebiological sample, such as anti-coagulants, such as heparin, sodiumcitrate, or EDTA.

The capillary channel has a first end 12 and a second end 13. The firstend 12 of the channel is adapted to draw fluid into the capillarychannel. In one preferred embodiment as shown in FIG. 2A, the first end12 opens on the side surface of the body 10A in order to simplify samplecollection from a live subject as describe in more detail below. Inanother preferred embodiment as shown in FIGS. 1, 3A and 3B, the firstend includes a sample collection well 14. The sample collection well 14preferably opens onto the top surface of the body and can simply be aconcavity in the top of the body. The collection well is preferablyhydrophilic to assist in acquiring and retaining the sample. Varioushydrophilic coatings and materials can be used to render the wellhydrophilic, including the same materials described with respect to thecapillary channel. In a preferred embodiment, the well is be sized tohold approximately the same volume as the channel, so as to preventpossible sample overload. The second end 13 includes an air vent 18 thatopens to the outside environment. In a preferred embodiment, the airvent is connected to a source of air pressure to pressurize thecapillary channel as described in more detail below. Located between thefirst and second end is a barrier 19 that prevents the flow of fluidacross it. This prevents, among other things, the fluid sample fromreaching the second end until it is ready for use and possibly leaking.The barrier can be selected from any material or construction thatprevents the flow of sample across it, until a source of air pressure isapplied. For example, the barrier can be a hydrophobic porous material,geometric features with sharp edges, a hydrophobic surface, orhydrophobic surface coating. The barrier allows air flow across it sothat the sample fluid in the capillary can be acted upon by applied airpressure.

The shape of the capillary channel can be straight or more preferably atleast partially non-linear. By having at least a non-linear portion themaximum gravitational forces which can act on the collected sample (withthe device in any orientation) are reduced, as compared to a sample in aconventional linear capillary tube of comparable type. In a preferredembodiment, the capillary channel has a serpentine shape as shown inFIG. 1A.

The body of the sample collection device includes features to form anaxis of rotation A as shown in FIG. 1. The features can be any type ofstructure that is capable of cooperating with features in the workingelement cartridge 30 to provide rotation around the axis A. In apreferred embodiment, the features are pins 50A, 50B that extendperpendicularly outward from the sides of the body to form the axis ofrotation A. Alternatively, the features can be corresponding protrusionsin the shape of slots to form the axis of rotation A.

The sample collection device is preferably part of a working element 20for performing some aspect of sample manipulation, such as a diagnosticassay, described in more detail below. Other sample manipulation couldinclude microfluidics devices that can be used to obtain a variety ofinteresting measurements including molecular diffusion coefficients,fluid viscosity, pH, chemical binding coefficients and enzyme reactionkinetics. Other applications for microfluidic devices include capillaryelectrophoresis, isoelectric focusing, flow cytometry, sample injectionof proteins for analysis via mass spectrometry, PCR amplification, DNAanalysis, cell manipulation, cell separation, cell patterning andchemical gradient formation.

The working element 20 includes a cartridge 30 for housing variouscomponents of the working element. FIG. 2A is a perspective view of theworking element 20 and its components. The sample collection device 10is located at a first end 21 of the test. When in the dispense position,the sample collection device is preferably fully contained within thecartridge 30 as shown in FIGS. 2B and 3A. Alternatively, when in thedispense position, the sample collection device 10 can be held withinthe cartridge housing such that a portion of the device 10 protrudesfrom the end 21 of the working element.

The device 10 sits within a groove or recess 31 that is formed withinthe cartridge 30 as shown in FIGS. 2A, 3B and 4. The groove 31preferably conforms to the shape of the collection device 10. If tabs orwings 17A, 17B are include, the groove will have corresponding recesses31A and 31B, as shown in FIGS. 3B and 4. In a preferred embodiment, thegroove terminates before the end of the cartridge housing 32 to form arecess 33 that extends through the entire thickness of the cartridgehousing as shown in FIG. 5. This allows for free rotation of the deviceabout axis of rotation A, when the device is in use.

The cartridge housing is preferably formed of two molded halves that canbe snap fit together or welded together. Alternatively, the cartridgehousing can include molded top cover and a laminated film.

As mentioned above, the cartridge housing includes features thatcooperate with the features on the body of the sample collection deviceto form the axis of rotation A. In a preferred embodiment, the featuresare slots 35A, 35B as shown in FIG. 5 that cooperate with pins 50 toform the axis of rotation. Alternatively, the cartridge housing caninclude pins that extend perpendicularly outward from the housing andcooperate with slots in the body of the sample collection device. Anyother features that provide an axis of rotation for the samplecollection device to rotate around can also be used. In a preferredembodiment, sample collection device is removably held in cartridge.This allows the sample collection device 10 to be provided separatelyfrom the rest of the working element 20. This is useful where differenttypes sample collection devices, e.g., with or without well 14, areemployed depending on the type of sample to be collected.

Other features of the cartridge housing can include an opening 34 thatprovides access to the sample manipulation device 40 of the workingelement. For example, if the sample manipulation device is a lateralflow diagnostic assay the opening 34 can be used to apply a wash fluidto the assay.

The sample collection device 10 is rotatably held within the cartridgehousing 30, whereby it can rotate around axis of rotation A betweenaspirate and dispense positions, or anywhere in-between.

The working element also includes a sample manipulation device 40 forconducting further analysis or processing of a sample. Such processingor analysis can include the microfluidics applications described above.As noted above, a particularly preferred sample manipulation is alateral flow diagnostic assay described in more detail below withreference to FIGS. 6-8. The sample manipulation device may include apre-manipulation portion 41, such as a filter for filtering whole blood.After application of the sample to the sample manipulation device 40,the working element can be further used in devices, such as an analyzerfor detecting and analyzing a signal, or a chemical processor forfurther processing of the sample, or any other type of microfluidicsdevices described above. A particularly preferred analyzer is afluorometer.

The sample manipulation device 40 and optionally the pre-manipulationportion 41 are in fluid communication with the sample collection device10 when it is in a dispense position as described below.

As noted above, the sample collection device is rotatable within thecartridge housing. This allows the device to move from a samplecollection or aspiration position as shown in FIG. 2A to a dispenseposition as shown in FIG. 2B where the sample can be dispensed to thesample manipulation device or pre-manipulation portion. In thecollection or aspirate position the first end 12 of the capillarychannel 11 is exposed to the outside environment, while the second end13 is within the cartridge housing. In the collection or aspirateposition the first end 12 can be directly contacted with the sample tobe collected, such as a drop of blood from a finger stick. By capillaryforces, the sample will be drawn or aspirated into the capillarychannel. Alternatively, the first end can include the sample collectionwell 14, which can have sample applied to it such as by a syringefilling the sample collection well 14. By capillary forces, the samplewill be drawn from the sample well into the capillary channel. Usingeither embodiment, the progression of the sample into the channel 11 canbe observed by a clear top portion 15A.

When a desired amount of sample has been collected, the samplecollection device can then be rotated to the dispense position as shownin FIGS. 2B and 3A. In the dispense position, the first end 12 of thecapillary channel is rotated to position it with the sample manipulationdevice 40 or pre-manipulation portion 41. A source of compressed air(not shown) is then applied to the second end 13 and the sample isforced to move from the capillary channel through the first end 12 andinto the sample manipulation device 40 or pre-manipulation 41 portion ofthe working element. The compressed air may be supplied by any suitablemeans, such as by a rubber diaphragm that may or may not be part of aninstrument or processing apparatus that further handles the workingelement.

Another aspect of the invention includes a method for collecting asample. A working element that includes the components described aboveis provided. The working element may include the sample collectiondevice already attached from the manufacturer. Alternatively, the samplecollection device may be provided separately. This allows the user toselect a first end 12 that either includes the sample collection well 14or not depending on how the sample is to be collected. If the samplecollection device is provided separately, the user will have to engagethe device with the end of the of cartridge 31. Preferably, slots andpins are provided as described above and the pins will fit in the slotswith a snapping engagement. In other words when the pins are insertedinto the slots, the pins and/or the slots will deform slightly in orderfor the larger diameter pins to pass through the top of the slots. Whenthe pins pass through the top of the slots, the pins and/or slots willquickly return to their original shape(s), resulting in a “snapping”sound. One significant advantage to having the sample collection deviceprovided separately is in the event sample is not collected properly,the user would simply use a new sample collection device and would nothave to replace the entire working element.

The sample collection device is then rotated into a collection oraspiration position, which is a direction extending away from thecartridge, as shown in FIG. 2A. The first end is then contacted withsample. As discussed above, if the sample to be collected is from a bodyof an animal, such as a finger stick of blood, the end preferably doesnot include the sample well 14. If the sample is already in anothercontainer, such as a syringe, then it is preferred to dispense thesample into the sample well 14. Capillary action will then draw thesample into the capillary channel 11.

The sample collection device 10 is then rotated about axis of rotation Ato bring the first end 12 into a dispense position, where the first endcontacts the sample manipulation device 40 or pre-manipulation portion41, such as a filter. Alternatively, the sample collection device can beheld at a position intermediate the collection position and dispenseposition, such as shown in FIG. 4. This may be useful, where the sampleis not ready to be dispensed. After, the sample collection device isrotated to the dispense position, air pressure is applied to the airvent 18 to force sample across the barrier 19 and into contact with thesample manipulation device or pre-manipulation portion.

In a preferred embodiment, the sample manipulation device of thecartridge or a cassette is a diagnostic assay. Diagnostic assays arewidespread and central for the diagnosis, treatment and management ofmany diseases. Different types of diagnostic assays have been developedover the years in order to simplify the detection of various analytes inclinical samples such as blood, serum, plasma, urine, saliva, tissuebiopsies, stool, sputum, skin or throat swabs and tissue samples orprocessed tissue samples. These assays are frequently expected to give afast and reliable result, while being easy to use and inexpensive tomanufacture.

Examples of diagnostic assays include, but are not limited to, thedetermination of analytes, also called markers, specific for differentdisorders, e.g. chronic metabolic disorders, such as blood glucose,blood ketones, urine glucose (diabetes), blood cholesterol(atherosclerosis, obesity, etc); markers of other specific diseases,e.g. acute diseases, such as coronary infarct markers (e.g. troponin-T,NT-ProBNP), markers of thyroid function (e.g. determination of thyroidstimulating hormone (TSH)), markers of viral infections (the use oflateral flow immunoassays for the detection of specific viralantibodies); etc.

Yet another important field is the field of companion diagnostics wherea therapeutic agent, such as a drug, is administered to an individual inneed of such a drug. An appropriate assay is then conducted to determinethe level of an appropriate marker to determine whether the drug ishaving its desired effect. Alternatively, the assay device of thepresent invention can be used prior to administration of a therapeuticagent to determine if the agent will help the individual in need.

Yet another important field is that of drug tests, for easy and rapiddetection of drugs and drug metabolites indicating drug abuse; such asthe determination of specific drugs and drug metabolites (e.g. THC) inurine samples etc.

The term “analyte” is used as a synonym of the term “marker” andintended to encompass any chemical or biological substance that ismeasured quantitatively or qualitatively and can include smallmolecules, proteins, antibodies, DNA, RNA, nucleic acids, viruscomponents or intact viruses, bacteria components or intact bacteria,cellular components or intact cells and complexes and derivativesthereof.

The term “reaction” is used to define any reaction, which takes placebetween components of a sample and at least one reagent or reagents onor in the substrate, or between two or more components present in thesample. The term “reaction” is in particular used to define thereaction, taking place between an analyte and a reagent as part of thequalitative or quantitative determination of the analyte.

The term “substrate” means the carrier or matrix to which a sample isadded, and on or in which the determination is performed, or where thereaction between analyte and reagent takes place.

A common type of disposable assay device includes a zone or area forreceiving the liquid sample, a conjugate zone also known as a reagentzone, and a reaction zone also known as a detection zone. These assaydevices are commonly known as lateral flow test strips. They employ aporous material, e.g., nitrocellulose, defining a path for fluid flowcapable of supporting capillary flow. Examples include those shown inU.S. Pat. Nos. 5,559,041, 5,714,389, 5,120,643, and 6,228,660 all ofwhich are incorporated herein by reference in their entireties.

The sample-addition zone frequently consists of a more porous material,capable of absorbing the sample, and, when separation of blood cells isdesired, also effective to trap the red blood cells. Examples of suchmaterials are fibrous materials, such as paper, fleece, gel or tissue,comprising e.g. cellulose, wool, glass fiber, asbestos, syntheticfibers, polymers, or mixtures of the same.

Another type of assay device is a non-porous assay having projections toinduce capillary flow. Examples of such assay devices include the openlateral flow device as disclosed in WO 2003/103835, WO 2005/089082, WO2005/118139, and WO 2006/137785, all of which are incorporated herein byreference in their entireties.

A non-porous assay device is shown in FIG. 6. The assay device 1, has atleast one sample addition zone 2, a reagent zone 3, at least onedetection zone 4, and at least one wicking zone 5. The zones form a flowpath by which sample flows from the sample addition zone to the wickingzone. Also included are capture elements, such as antibodies, in thedetection zone 4, capable of binding to the analyte, optionallydeposited on the device (such as by coating); and a labeled conjugatematerial also capable of participating in reactions that will enabledetermination of the concentration of the analyte, deposited on thedevice in the reagent zone, wherein the labeled conjugate materialcarries a label for detection in the detection zone. The conjugatematerial is dissolved as the sample flows through the reagent zoneforming a conjugate plume of dissolved labeled conjugate material andsample that flows downstream to the detection zone. As the conjugateplume flows into the detection zone, the conjugated material will becaptured by the capture elements such as via a complex of conjugatedmaterial and analyte (as in a “sandwich” assay) or directly (as in a“competitive” assay. Unbound dissolved conjugate material will be sweptpast the detection zone into the at least one wicking zone 5.

An instrument such as that disclosed in US 20060289787A1,US20070231883A1, U.S. Pat. No. 7,416,700 and U.S. Pat. No. 6,139,800 allincorporated by reference in their entireties is able to detect thebound conjugated analyte and label in the reaction zone. Common labelsinclude fluorescent dyes that can be detected by instruments whichexcite the fluorescent dyes and incorporate a detector capable ofdetecting the fluorescent dyes. Such instruments have a read window thathas a width that is typically on the order of 1 mm, which is a generallysufficient width to read enough signal, subject to an adequate width ofthe conjugate plume.

FIG. 7 shows a schematic view of a preferred lateral flow assay deviceusable as the sample manipulation device 40. The assay device 100 has atleast one sample zone (also referred to as sample addition zone) 200, atleast one reagent zone 300, at least one detection zone 400, and atleast one wicking zone 500. The zones form a flow path by which sampleflows from the sample addition zone to the wicking zone.

Components of the assay device and any other part of the working element(i.e., a physical structure of the device whether or not a discretepiece from other parts of the device) can be prepared from copolymers,blends, laminates, metalized foils, metalized films or metals.Alternatively, device components can be prepared from copolymers,blends, laminates, metalized foils, metalized films or metals depositedone of the following materials: polyolefins, polyesters, styrenecontaining polymers, polycarbonate, acrylic polymers, chlorinecontaining polymers, acetal homopolymers and copolymers, cellulosics andtheir esters, cellulose nitrate, fluorine containing polymers,polyamides, polyimides, polymethylmethacrylates, sulfur containingpolymers, polyurethanes, silicon containing polymers, glass, and ceramicmaterials. Alternatively, components of the device are made with aplastic, elastomer, latex, silicon chip, or metal; the elastomer cancomprise polyethylene, polypropylene, polystyrene, polyacrylates,silicon elastomers, or latex. Alternatively, components of the devicecan be prepared from latex, polystyrene latex or hydrophobic polymers;the hydrophobic polymer can comprise polypropylene, polyethylene, orpolyester. Alternatively, components of the device can comprise TEFLON®,polystyrene, polyacrylate, or polycarbonate. Alternatively, devicecomponents are made from plastics which are capable of being embossed,milled or injection molded or from surfaces of copper, silver and goldfilms upon which may be adsorbed various long chain alkanethiols. Thestructures of plastic which are capable of being milled or injectionmolded can comprise a polystyrene, a polycarbonate, or a polyacrylate.In a particularly preferred embodiment, the assay device is injectionmolded from a cyclo olefin polymer, such as those sold under the nameZeonor®. Preferred injection molding techniques are described in U.S.Pat. Nos. 6,372,542, 6,733,682, 6,811,736, 6,884,370, and 6,733,682, allof which are incorporated herein by reference in their entireties.

The flow path can include open or closed paths, grooves, andcapillaries. Preferably the flow path comprises a lateral flow path ofadjacent projections, having a size, shape and mutual spacing such thatcapillary flow is sustained through the flow path. In one embodiment,the flow path is in a channel within the substrate having a bottomsurface and side walls. In this embodiment, the projections protrudefrom the bottom surface of the channel. The side walls may or may notcontribute to the capillary action of the liquid. If the sidewalls donot contribute to the capillary action of the liquid, then a gap can beprovided between the outermost projections and the sidewalls to keep theliquid contained in the flow path defined by the projections. FIG. 6shows projections 7.

In one embodiment the flow path is at least partially open. In anotherembodiment the flow path is entirely open. Open means that there is nolid or cover at a capillary distance. Thus the cover, if present as aphysical protection for the flow path, does not contribute to thecapillary flow in the flow path. An open lateral flow path is describedfor example in the following published applications: WO 2003/103835, WO2005/089082; WO 2005/118139; WO 2006/137785; and WO 2007/149042, all ofwhich are incorporated by reference in their entireties. The projectionshave a height (H), diameter (D) and a distance or distances between theprojections (t1, t2) such, that lateral capillary flow of the fluid,such as plasma, preferably human plasma, in the zone is achieved. Thesedimensions are shown in US 2006/0285996, which is incorporated byreference in its entirety. In addition to optimizing the above-mentionedheight, diameter and a distance or distances between the projections,the projections may be given a desired chemical, biological or physicalfunctionality, e.g. by modifying the surface of the projections. In oneembodiment, the projections have a height in the interval of about 15 toabout 150 μm, preferably about 30 to about 100 μm, a diameter of about10 to about 160 μm, preferably 40 to about 100 μm, and a gap or gapsbetween the projections of about 3 to about 200 μm, preferably 5 toabout 50 μm or 10 to 50 μm from each other. The flow channel may have alength of about 5 to about 500 mm, preferably about 10 to about 100 mm,and a width of about 0.3 to about 10 mm, preferably about 0.3 to about 3mm, preferably about 0.5 to 1.5, and preferably about 0.5 to 1.2 mm.

While most detection will occur in the detection zone portion of thefluid flow path, it is also possible that detection may occur in otherparts of the device. For example, non-invasive, non-reactive sampleintegrity measurements may occur between the sample zone and the reagentzone or reagent addition zone, preferably after a filter element, ifpresent. Other measurements may include blanks reads, one part of a twopart reaction sequence as for measuring both hemoglobin and glycatedhemoglobin for determination of HbA1c, etc.

The liquid sample zone 200, also referred to as the liquid sampleaddition zone, receives sample from the sample collection device 10. Thesample addition zone is capable of transporting the liquid sample fromthe point where the sample is deposited to the reagent zone, through anoptional filter and reagent addition zone, preferably through capillaryflow. The capillary flow inducing structure can include porousmaterials, such as nitrocellulose, or preferably through projections,such as micro-pillars, as shown in FIG. 6. In those devices that can usefinger stick volumes of blood, the sample can be directly touched offfrom the finger, or by a capillary pipette.

Located between the sample addition zone and the detection zone is areagent zone 300. The reagent zone can include reagent material(s)integrated into the analytical element and are generally reagents usefulin the reaction—binding partners such as antibodies or antigens forimmunoassays, substrates for enzyme assays, probes for moleculardiagnostic assays, or are auxiliary materials such as materials thatstabilize the integrated reagents, materials that suppress interferingreactions, etc. Generally one of the reagents useful in the reactionbears a detectable signal as discussed below. In some cases the reagentsmay react with the analyte directly or through a cascade of reactions toform a detectable signal such as, but not restricted to, a moleculedetectable using spectroscopy such as a colored or fluorescent molecule.In one preferred embodiment, the reagent zone includes conjugatematerial. The term conjugate means any moiety bearing both a detectionelement and a binding partner.

The detection element is an agent which is detectable with respect toits physical distribution or/and the intensity of the signal itdelivers, such as but not limited to luminescent molecules (e.g.fluorescent agents, phosphorescent agents, chemiluminescent agents,bioluminescent agents and the like), colored molecules, moleculesproducing colors upon reaction, enzymes, radioisotopes, ligandsexhibiting specific binding and the like. The detection element alsoreferred to as a label is preferably chosen from chromophores,fluorophores, radioactive labels, and enzymes. Suitable labels areavailable from commercial suppliers, providing a wide range of dyes forthe labeling of antibodies, proteins, and nucleic acids. There are, forexample, fluorophores spanning practically the entire visible andinfrared spectrum. Suitable fluorescent or phosphorescent labels includefor instance, but are not limited to, fluoresceins, Cy3, Cy5 and thelike. Suitable chemoluminescent labels are for instance but are notlimited to luminol, cyalume and the like.

Similarly, radioactive labels are commercially available, or detectionelements can be synthesized so that they incorporate a radioactivelabel. Suitable radioactive labels are for instance but are not limitedto radioactive iodine and phosphorus; e.g. ¹²⁵I and ³²P.

Suitable enzymatic labels are, for instance, but are not limited to,horseradish peroxidase, beta-galactosidase, luciferase, alkalinephosphatase and the like. Two labels are “distinguishable” when they canbe individually detected and preferably quantified simultaneously,without significantly disturbing, interfering or quenching each other.Two or more labels may be used, for example, when multiple analytes ormarkers are being detected.

The binding partner is a material that can form a complex that can beused to determine the presence of or amount of an analyte. For example,in an “sandwich” assay, the binding partner in the conjugate can form acomplex including the analyte and the conjugate and that complex canfurther bind to another binding partner, also called a capture element,integrated into the detection zone. In a competitive immunoassay, theanalyte will interfere with binding of the binding partner in theconjugate to another binding partner, also called a capture element,integrated into the detection zone. Example binding partners included inconjugates include antibodies, antigens, analyte or analyte-mimics,protein, etc.

Optionally located in the fluid flow path, before or after the reagentzone and before the detection zone is a reagent addition zone. Thereagent addition zone is shown as 350 in FIG. 8. The reagent additionzone can allow addition of a reagent externally from the device. Forexample, the reagent addition zone may be used to add an interruptingreagent that may be used to wash the sample and other unbound componentspresent in the fluid flow path into the wicking zone. In a preferredembodiment the reagent addition zone 350 is located after the reagentzone 300.

Downstream from the liquid sample zone and the reagent zone is thedetection zone 400 which is in fluid communication with the sampleaddition zone. The detection zone 400 may include projections such asthose described above. As also noted above, these projections arepreferably integrally molded into the substrate from an optical plasticmaterial such as Zeonor, such as injection molding or embossing. Thewidth of the flow channel in the detection zone is typically on theorder of 2 mm for conventional size devices, however, some lower volumedevices, such as those described above and in co pending applicationentitled “Lower Volume Assay Device Having Increased Sensitivity,” Ser.No. 13/744,617, filed on Jan. 20, 2013 and incorporated by reference inits entirety, are significantly narrower, e.g., 1.5 mm or less,preferably 0.5 to 1.2 mm.

The detection zone is where any detectable signal is read. In apreferred embodiment attached to the projections in the detection zoneare capture elements. The capture elements can include binding partnersfor the conjugate or complexes containing the conjugate, as describedabove. For example, if the analyte is a specific protein, the conjugatemay be an antibody that will specifically bind that protein coupled to adetection element such as a fluorescence probe. The capture elementcould then be another antibody that also specifically binds to thatprotein. In another example, if the marker or analyte is DNA, thecapture molecule can be, but is not limited to, syntheticoligonucleotides, analogues thereof, or specific antibodies. Othersuitable capture elements include antibodies, antibody fragments,aptamers, and nucleic acid sequences, specific for the analyte to bedetected. A non-limiting example of a suitable capture element is amolecule that bears avidin functionality that would bind to a conjugatecontaining a biotin functionality. The detection zone can includemultiple detection zones. The multiple detection zones can be used forassays that include one or more markers. In the event of multipledetection zones, the capture elements can include multiple captureelements, such as first and second capture elements. The conjugate canbe pre-deposited on the assay device, such as by coating in the reagentzone. Similarly the capture elements can be pre-deposited on the assaydevice on the detection zone. Preferably, both the detection and captureelements are pre-deposited on the assay device, on the detection zoneand detection zone, respectively.

After the sample has been delivered to the sample zone, it willencounter the reagent zone. After the sample has flowed through andinteracted with the reagent zone and optionally the reagent additionzone, the sample and a reagent plume will be contained in the fluidflow. The reagent plume can contain any of the reagent materials thathave been dissolved in the detection zone or those added through thereagent addition zone. The reagent in the sample flowing from thereagent zone, but before the reagent addition zone is considered to be areagent plume. The reagent plume can include the conjugate having boththe detection element and binding partner, in which case it is oftenreferred to as a conjugate plume.

Downstream from the detection zone is a wicking zone in fluidcommunication with the detection zone. The wicking zone is an area ofthe assay device with the capacity of receiving liquid sample and anyother material in the flow path, e.g., unbound reagents, wash fluids,etc. The wicking zone provides a capillary force to continue moving theliquid sample through and out of the detection zone. The wicking zonecan include a porous material such as nitrocellulose or can be anon-porous structure such as the projections described herein. Thewicking zone can also include non-capillary fluid driving means, such asusing evaporative heating or a pump. Further details of wicking zones asused in assay devices according to the present invention can be found inpatent publications US 2005/0042766 and US 2006/0239859, both of whichare incorporated herein by reference in their entireties. Wicking zonesare also described in copending patent application entitled “ControllingFluid Flow Through An Assay Device,” Ser. No. 13/744,641, filed on Jan.18, 2013, and incorporated by reference in its entirety.

Preferably the entirety of the flow path including the sample additionzone, the detection zone and the wicking zone includes projectionssubstantially vertical in relation to the substrate, and having aheight, diameter and reciprocal spacing capable of creating lateral flowof the sample in the flow path.

In any of the above embodiments, the device is preferably a disposableassay device. The assay device may be contained in a housing for ease ofhandling and protection. If the assay device is contained in such ahousing, the housing will preferably include a port for adding sample tothe assay device.

The assay device of the present invention can be used with a device forreading (a reader) the result of an assay device performed on the assayof the present invention. The reader includes means for reading a signalemitted by, or reflected from the detection element, such as aphotodetector, and means for computing the signal and displaying aresult, such as microprocessor that may be included within an integratedreader or on a separate computer. Suitable readers are described forexample in US 2007/0231883 and U.S. Pat. No. 7,416,700, both of whichare incorporated by reference in their entireties.

Another embodiment is a device for reading the result of an assayperformed on an assay device, wherein the device comprises a detectorcapable of reading a signal emitted from or reflected from at least onedetection element present in a defined location of the assay device. Ineither of the above embodiments, the reading preferably is chosen fromthe detection and/or quantification of color, fluorescence,radioactivity or enzymatic activity.

The assay device along with the rest of the cartridge can be used toperform an assay on a liquid sample for the detection of one or moreanalytes of interest. A liquid sample containing the analyte(s) ofinterest is collected using the sample collection device as describedabove and is then dispensed onto the sample zone of the assay device.The sample moves by capillary action through an optional filter and intothe reagent zone where it encounters the multiple reagent materials. Thesample flows past the first, second and third reagent material. Thereagent material flowing past the second and third reagent materialsform second and third reagent plumes along the edges of the reagentcell. The sample flowing past the first reagent material forms a firstreagent plume long the line of symmetry of the reagent cell. The first,second and third reagent material combine upon leaving the reagent cellto form a combined reagent plume.

Next the sample and reagent plume move by capillary action into thedetection zone. There a signal representative of the presence orconcentration of the analyte(s) or control is produced. In a preferredembodiment the sample or the one or more reagents having a detectionelement is captured having in the detection zone, such as by antibodieson the surface of the detection zone and a signal representative of thepresence or concentration of the analyte(s) or control(s) is produced.

The reader as described above is then used to read the signal that isproduced by the detection element to determine the presence orconcentration of the analyte(s). The sample moves from the detectionzone and into the wicking zone. The reader may read the signalimmediately or a short time after the sample has moved through thedetection zone. Also, one or more washes may follow the sample throughthe device to wash any unbound detection element away from the detectionzone. The cartridge 20 containing the lateral flow assay device can beinserted into the reader either before or after the sample has beendispensed to the sample zone. In those embodiments where a source ofcompressed air is used to dispense the sample, the cartridge can firstbe inserted into the reader and the compressed air can then be used toforce sample from the sample collection device to the assay device.

The method, assay device, and reader according to an embodiment of theinvention have many advantages, mainly related to the improved detectionkinetics of the immunochemical reactions and the increased sensitivityof the assay. It is to be understood that this invention is not limitedto the particular embodiments shown here.

Additional Embodiments

1. A sample collection device for a fluid sample, the device comprising:a body including a capillary channel having a first end and a secondend, wherein the first end is adapted to draw the fluid into the channelby capillary action; an air vent located in the vicinity of the secondend and in fluid communication with the capillary channel; a barrierpositioned within the capillary channel to prevent flow of the fluid bycapillary action there across; and features on opposing sides of thebody to form an axis of rotation, which is substantially perpendicularto the overall direction of the capillary channel from the first end tothe second end.

2. A sample collection device as disclosed in embodiment 1, wherein thesample collection device is adapted to rotate about the axis of rotationwithin a cartridge having a sample manipulation device to bring thefirst end into position with the sample manipulation device.

3. A sample collection device as disclosed in embodiment 1, wherein atleast a portion of the capillary channel is non-linear.

4. A sample collection device as disclosed in embodiment 1, wherein thebarrier comprises a portion of the surface of the channel that ishydrophobic.

5. A sample collection device as disclosed in embodiment 1, whereinfirst end of the channel is hydrophilic.

6. A sample collection device as disclosed in embodiment 5, wherein thefirst end is provided with a hydrophilic coating.

7. A sample collection device as disclosed in embodiment 1, wherein thebody has a substantially rectangular shape, and wherein the first end islocated at the first shorter dimension and the second end is located inthe vicinity of the second shorter dimension.

8. A sample collection device as disclosed in embodiment 7, wherein thefeatures on opposing sides of the body are located on the longerdimensions.

9. A sample collection device as disclosed in embodiment 8, wherein thefeatures are projections extending outwardly from the body.

10. A sample collection device as disclosed in embodiment 1, wherein thebarrier is selected from the group consisting of a hydrophobic porousmaterial, geometric features with sharp edges, a hydrophobic surface, orhydrophobic surface coating, whereby the barrier allows air flow to thecapillary channel so that the sample in the capillary can be acted uponby applied air pressure.

11. A working element comprising: a sample collection device for asample fluid, the device comprising: a body including a capillarychannel having a first end and a second end, wherein the first end isadapted to draw the fluid into the channel by capillary action; an airvent located in the vicinity of the second end and in fluidcommunication with the capillary channel; a barrier positioned withinthe capillary channel to prevent flow of the fluid by capillary actionthereacross; and features on opposing sides of the body; and a cartridgehaving a sample manipulation device, wherein the cartridge has featuresthat correspond to features on the sample collection device to form anaxis of rotation, which is substantially perpendicular to the overalldirection of the capillary channel from the first end to the second endabout which the sample collection device rotates, and wherein the samplecollection device is adapted to rotate about the axis of rotation tobring the first end into position with the sample manipulation device.

12. A working element as disclosed in embodiment 11, wherein the samplemanipulation device includes at least one filter in fluid communicationwith the first end of the capillary channel.

13. A working element as disclosed in embodiment 11, wherein the samplemanipulation device is an analytical chamber in fluid communication withthe first end of the capillary channel.

14. A working element as disclosed in embodiment 13, wherein theanalytical chamber is provided with an analytical reagent thereon.

15. A working element as disclosed in embodiment 14, wherein theanalytical chamber is a lateral flow assay device.

16. A working element as disclosed in embodiment 11, wherein the bodyhas a substantially rectangular shape, and wherein the first end islocated at the first shorter dimension and the second end is located inthe vicinity of the second shorter dimension.

17. A working element as disclosed in embodiment 11, wherein the samplecollection device is located at a first end of the cartridge housing.

18. A working element as disclosed in embodiment 17, wherein a portionof the cartridge has a groove which at least partially contains thesample collection device.

19. A working element as disclosed in embodiment 17, wherein the bodyhas a substantially rectangular shape, and wherein the first end islocated at the first shorter dimension and the second end is located inthe vicinity of the second shorter dimension.

20. A working element as disclosed in embodiment 19, wherein thefeatures of the cartridge that form the axis of rotation are located inthe portion of the housing that forms the groove or a recess within thegroove, whereby the sample collection device rotates from a positionwhere the first end extends away from the cartridge to a position wherethe first end is in contact with the sample manipulation device.

21. A working element as disclosed in embodiment 18, the features of thesample collection device comprise pins and the features of the cartridgehousing comprise slots which cooperate with the pins to form the axis ofrotation.

22. A method for collecting a fluid sample comprising: providing aworking element which comprises: a sample collection device for a fluidsample, the device comprising: a body including a capillary channelhaving a first end and a second end, wherein the first end is adapted todraw the fluid into the channel by capillary action; an air vent locatedin the vicinity of the second end and in fluid communication with thecapillary channel; a barrier positioned within the capillary channel toprevent flow of the fluid by capillary action thereacross; and featureson opposing sides of the body; and a cartridge having a samplemanipulation device, wherein the cartridge has features that correspondto features on the sample collection device to form an axis of rotation,which is substantially perpendicular to the overall direction of thecapillary channel from the first end to the second end about which thesample collection device rotates, and wherein the sample collectiondevice is adapted to rotate about the axis of rotation to bring thefirst end into position with the sample manipulation device; rotatingthe sample collection device to position the first end in a directionextending away from the cartridge; bringing the first end into contactwith the sample, whereby capillary action draws the sample into thechannel and to the barrier; rotating the sample collection device toposition the first end into position with the sample manipulationdevice; and applying air pressure to the air vent to force the sampleacross the barrier and into contact with the sample manipulation device.

23. A method as disclosed in embodiment 22, wherein the sample is anaqueous fluid sample.

24. A sample collection device as disclosed in embodiment 23, whereinthe fluid is a bodily fluid.

25. A method of as disclosed in embodiment 23, wherein the sample iswhole blood, serum, plasma or urine.

26. A method as disclosed in embodiment 22, wherein the step of bringingthe first end into contact with the sample comprises bringing the firstend into contact with a drop of blood on an animal.

27. A method as disclosed in embodiment 26, wherein the animal is amammal.

28. A method as disclosed in embodiment 27, wherein the mammal is ahuman.

29. A method as disclosed in embodiment 22, wherein the step of bringingthe first end into contact with the sample comprises bringing the firstend into contact with a syringe containing blood from an animal.

30. A method as disclosed in embodiment 22, wherein the samplemanipulation device includes a sample pre-manipulation portioncomprising at least one filter in fluid communication with the first endof the capillary channel.

31. A method as disclosed in embodiment 22, wherein the samplemanipulation device is an analytical chamber in fluid communication withthe first end of the capillary channel.

32. A method as disclosed in embodiment 31, wherein the analyticalchamber is provided with an analytical reagent.

33. A method as disclosed in embodiment 22, wherein the body has asubstantially rectangular shape, and wherein the first end is located atthe first shorter dimension and the second end is located in thevicinity of the second shorter dimension.

34. A method as disclosed in embodiment 22, wherein the samplecollection device is located at a first end of the cartridge housing.

35. A method as disclosed in embodiment 34, wherein a portion of thecartridge housing has a groove which contains the sample collectiondevice.

36. A method as disclosed in embodiment 35, wherein the body has asubstantially rectangular shape, and wherein the first end is located atthe first shorter dimension and the second end is located in thevicinity of the second shorter dimension.

37. A method as disclosed in embodiment 36, wherein the features of thecartridge that form the axis of rotation are located in the portion ofthe housing that forms the groove or a recess in the groove, whereby thesample collection device rotates from a position where the first endextends away from the cartridge to a position where the first end is incontact with the sample manipulation device.

38. A method of performing an assay on a liquid sample for the presenceor concentration of one or more analyte(s) or control(s), on the assaydevice according to embodiment 15, comprising: rotating the samplecollection device to position the first end in a direction extendingaway from the cartridge; bringing the first end into contact with thesample, whereby capillary action draws the sample into the channel andto the barrier; rotating the sample collection device to position thefirst end into position with assay device; applying air pressure to theair vent to force the sample across the barrier and into contact with asample addition zone of the assay device; moving the sample by capillaryaction through a fluid flow path into a reagent zone where it dissolvesone or more reagents; flowing the sample away from the reagent zonehaving a dissolved reagent plume containing one or more reagents andinto detection zone(s) by capillary action through the fluid flow path,wherein signal(s) representative of the presence or concentration ofanalyte(s) or control(s) is produced; and reading the signal(s) that areproduced in the detection zones to determine the presence orconcentration of the analytes or controls.

Those skilled in the art will appreciate that the invention andembodiments thereof described herein are susceptible to variations andmodifications other than those specifically described. It is to beunderstood that the invention includes all such variations andmodifications. The invention also includes all of the steps and featuresreferred to in this specification, individually or collectively, and anyand all combinations of any two or more of the steps or features.

What is claimed is:
 1. A sample collection device for a fluid sample,the device comprising: a body including a capillary channel having afirst end and a second end, wherein the first end is adapted to draw thefluid into the channel by capillary action; an air vent located in thevicinity of the second end and in fluid communication with the capillarychannel; a barrier positioned within the capillary channel to preventflow of the fluid by capillary action thereacross; and features onopposing sides of the body to form an axis of rotation, which issubstantially perpendicular to the overall direction of the capillarychannel from the first end to the second end.
 2. A sample collectiondevice as claimed in claim 1, wherein the sample collection device isadapted to rotate about the axis of rotation within a cartridge having asample manipulation device to bring the first end into position with thesample manipulation device.
 3. A sample collection device as claimed inclaim 1, wherein at least a portion of the capillary channel isnon-linear.
 4. A sample collection device as claimed in claim 1, whereinthe barrier comprises a portion of the surface of the channel that ishydrophobic.
 5. A sample collection device as claimed in claim 1,wherein first end of the channel is hydrophilic.
 6. A sample collectiondevice as claimed in claim 5, wherein the first end is provided with ahydrophilic coating.
 7. A sample collection device as claimed in claim1, wherein the body has a substantially rectangular shape, and whereinthe first end is located at the first shorter dimension and the secondend is located in the vicinity of the second shorter dimension.
 8. Asample collection device as claimed in claim 7, wherein the features onopposing sides of the body are located on the longer dimensions.
 9. Asample collection device as claimed in claim 8, wherein the features areprojections extending outwardly from the body.
 10. A sample collectiondevice as claimed in claim 1, wherein the barrier is selected from thegroup consisting of a hydrophobic porous material, geometric featureswith sharp edges, a hydrophobic surface, or hydrophobic surface coating,whereby the barrier allows air flow to the capillary channel so that thesample in the capillary can be acted upon by applied air pressure.
 11. Aworking element comprising: a sample collection device for a samplefluid, the device comprising: a body including a capillary channelhaving a first end and a second end, wherein the first end is adapted todraw the fluid into the channel by capillary action; an air vent locatedin the vicinity of the second end and in fluid communication with thecapillary channel; a barrier positioned within the capillary channel toprevent flow of the fluid by capillary action thereacross; and featureson opposing sides of the body; and a cartridge having a samplemanipulation device, wherein the cartridge has features that correspondto features on the sample collection device to form an axis of rotation,which is substantially perpendicular to the overall direction of thecapillary channel from the first end to the second end about which thesample collection device rotates, and wherein the sample collectiondevice is adapted to rotate about the axis of rotation to bring thefirst end into position with the sample manipulation device.
 12. Aworking element as claimed in claim 11, wherein the sample manipulationdevice includes at least one filter in fluid communication with thefirst end of the capillary channel.
 13. A working element as claimed inclaim 11, wherein the sample manipulation device is an analyticalchamber in fluid communication with the first end of the capillarychannel.
 14. A working element as claimed in claim 13, wherein theanalytical chamber is provided with an analytical reagent thereon.
 15. Aworking element as claimed in claim 14, wherein the analytical chamberis a lateral flow assay device.
 16. A working element as claimed inclaim 11, wherein the body has a substantially rectangular shape, andwherein the first end is located at the first shorter dimension and thesecond end is located in the vicinity of the second shorter dimension.17. A working element as claimed in claim 11, wherein the samplecollection device is located at a first end of the cartridge housing.18. A working element as claimed in claim 17, wherein a portion of thecartridge has a groove which at least partially contains the samplecollection device.
 19. A working element as claimed in claim 17, whereinthe body has a substantially rectangular shape, and wherein the firstend is located at the first shorter dimension and the second end islocated in the vicinity of the second shorter dimension.
 20. A workingelement as claimed in claim 19, wherein the features of the cartridgethat form the axis of rotation are located in the portion of the housingthat forms the groove or a recess within the groove, whereby the samplecollection device rotates from a position where the first end extendsaway from the cartridge to a position where the first end is in contactwith the sample manipulation device.
 21. A working element as claimed inclaim 18, the features of the sample collection device comprise pins andthe features of the cartridge housing comprise slots which cooperatewith the pins to form the axis of rotation.
 22. A method for collectinga fluid sample comprising: providing a working element which comprises:a sample collection device for a fluid sample, the device comprising: abody including a capillary channel having a first end and a second end,wherein the first end is adapted to draw the fluid into the channel bycapillary action; an air vent located in the vicinity of the second endand in fluid communication with the capillary channel; a barrierpositioned within the capillary channel to prevent flow of the fluid bycapillary action thereacross; and features on opposing sides of thebody; and a cartridge having a sample manipulation device, wherein thecartridge has features that correspond to features on the samplecollection device to form an axis of rotation, which is substantiallyperpendicular to the overall direction of the capillary channel from thefirst end to the second end about which the sample collection devicerotates, and wherein the sample collection device is adapted to rotateabout the axis of rotation to bring the first end into position with thesample manipulation device; rotating the sample collection device toposition the first end in a direction extending away from the cartridge;bringing the first end into contact with the sample, whereby capillaryaction draws the sample into the channel and to the barrier; rotatingthe sample collection device to position the first end into positionwith the sample manipulation device; and applying air pressure to theair vent to force the sample across the barrier and into contact withthe sample manipulation device.
 23. A method as claimed in claim 22,wherein the sample is an aqueous fluid sample.
 24. A sample collectiondevice as claimed in claim 23, wherein the fluid is a bodily fluid. 25.A method of as claimed in claim 23, wherein the sample is whole blood,serum, plasma or urine.
 26. A method as claimed in claim 22, wherein thestep of bringing the first end into contact with the sample comprisesbringing the first end into contact with a drop of blood on an animal.27. A method as claimed in claim 26, wherein the animal is a mammal. 28.A method as claimed in claim 27, wherein the mammal is a human.
 29. Amethod as claimed in claim 22, wherein the step of bringing the firstend into contact with the sample comprises bringing the first end intocontact with a syringe containing blood from an animal.
 30. A method asclaimed in claim 22, wherein the sample manipulation device includes asample pre-manipulation portion comprising at least one filter in fluidcommunication with the first end of the capillary channel.
 31. A methodas claimed in claim 22, wherein the sample manipulation device is ananalytical chamber in fluid communication with the first end of thecapillary channel.
 32. A method as claimed in claim 31, wherein theanalytical chamber is provided with an analytical reagent.
 33. A methodas claimed in claim 22, wherein the body has a substantially rectangularshape, and wherein the first end is located at the first shorterdimension and the second end is located in the vicinity of the secondshorter dimension.
 34. A method as claimed in claim 22, wherein thesample collection device is located at a first end of the cartridgehousing.
 35. A method as claimed in claim 34, wherein a portion of thecartridge housing has a groove which contains the sample collectiondevice.
 36. A method as claimed in claim 35, wherein the body has asubstantially rectangular shape, and wherein the first end is located atthe first shorter dimension and the second end is located in thevicinity of the second shorter dimension.
 37. A method as claimed inclaim 36, wherein the features of the cartridge that form the axis ofrotation are located in the portion of the housing that forms the grooveor a recess in the groove, whereby the sample collection device rotatesfrom a position where the first end extends away from the cartridge to aposition where the first end is in contact with the sample manipulationdevice.
 38. A method of performing an assay on a liquid sample for thepresence or concentration of one or more analyte(s) or control(s), onthe assay device according to claim 15, comprising: rotating the samplecollection device to position the first end in a direction extendingaway from the cartridge; bringing the first end into contact with thesample, whereby capillary action draws the sample into the channel andto the barrier; rotating the sample collection device to position thefirst end into position with assay device; applying air pressure to theair vent to force the sample across the barrier and into contact with asample addition zone of the assay device; moving the sample by capillaryaction through a fluid flow path into a reagent zone where it dissolvesone or more reagents; flowing the sample away from the reagent zonehaving a dissolved reagent plume containing one or more reagents andinto detection zone(s) by capillary action through the fluid flow path,wherein signal(s) representative of the presence or concentration ofanalyte(s) or control(s) is produced; and reading the signal(s) that areproduced in the detection zones to determine the presence orconcentration of the analytes or controls.